Adoptive Transfer of ILC2s Reveals Tumor Homing in Glioblastoma: A Proof-of-Concept Study

Lei Wang^*Bidhan BhandariSahar Emami NaeiniJack C YuAli Syed ArbabNancy YoungÉvila da Silva Lopes SallesBabak Baban^*

• Augusta University, Augusta, United States

Abstract Introduction: Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options and poor immune cell infiltration. Although cellular immunotherapies have transformed cancer treatment, they remain largely ineffective against GBM due to the restrictive blood–brain barrier (BBB) and a profoundly immunosuppressive tumor microenvironment. Innate lymphoid cells type 2 (ILC2s) have recently emerged as potential candidates for immune-based approaches because of their regenerative and immunomodulatory functions. Methods: Bone marrow–derived ILC2s from C57BL/6 mice were fluorescently labeled and intravenously transferred into hosts bearing orthotopic, luciferase-expressing GL261 glioblastoma tumors. Immune cell localization was assessed using fluorescence imaging and flow cytometric analyses of brain, tumor tissue, meninges, and peripheral organs. Results: Systemically administered ILC2s accessed the CNS and were detected within intracranial glioblastoma tumors and meninges. Transferred ILC2s localized to tumor tissue and meninges and were also identified in peripheral organs, demonstrating effective trafficking and tumor homing in an immunocompetent model. No measurable reduction in tumor growth was observed. Conclusion: These findings establish a proof-of-concept that adoptively transferred ILC2s can access and localize within glioblastoma in vivo. While not associated with tumor growth inhibition in this study, the results provide foundational insight into innate immune cell trafficking to central nervous system tumors and support further investigation into the immunomodulatory potential of ILC2s in GBM.